{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T13:43:33Z","timestamp":1790343813561,"version":"4.1.0"},"reference-count":68,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hungarian Brain Research Program 2.0","award":["2017-2.1 NKP 2017 00002"],"award-info":[{"award-number":["2017-2.1 NKP 2017 00002"]}]},{"name":"EU-funded Hungarian grant EFOP","award":["3.6.1-16-2016-00008"],"award-info":[{"award-number":["3.6.1-16-2016-00008"]}]},{"name":"GINOP","award":["2.3.2 15 2016 00034"],"award-info":[{"award-number":["2.3.2 15 2016 00034"]}]},{"name":"National Research, Development and Innovation Office","award":["OTKA-PD128464"],"award-info":[{"award-number":["OTKA-PD128464"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hypoxic\u2013ischemic encephalopathy (HIE) remains to be a major cause of long-term neurodevelopmental deficits in term neonates. Hypothermia offers partial neuroprotection warranting research for additional therapies. Kynurenic acid (KYNA), an endogenous product of tryptophan metabolism, was previously shown to be beneficial in rat HIE models. We sought to determine if the KYNA analog SZR72 would afford neuroprotection in piglets. After severe asphyxia (pHa = 6.83 \u00b1 0.02, \u0394BE = \u221217.6 \u00b1 1.2 mmol\/L, mean \u00b1 SEM), anesthetized piglets were assigned to vehicle-treated (VEH), SZR72-treated (SZR72), or hypothermia-treated (HT) groups (n = 6, 6, 6; Tcore = 38.5, 38.5, 33.5 \u00b0C, respectively). Compared to VEH, serum KYNA levels were elevated, recovery of EEG was faster, and EEG power spectral density values were higher at 24 h in the SZR72 group. However, instantaneous entropy indicating EEG signal complexity, depression of the visual evoked potential (VEP), and the significant neuronal damage observed in the neocortex, the putamen, and the CA1 hippocampal field were similar in these groups. In the caudate nucleus and the CA3 hippocampal field, neuronal damage was even more severe in the SZR72 group. The HT group showed the best preservation of EEG complexity, VEP, and neuronal integrity in all examined brain regions. In summary, SZR72 appears to enhance neuronal activity after asphyxia but does not ameliorate early neuronal damage in this HIE model.<\/jats:p>","DOI":"10.3390\/ijms22094822","type":"journal-article","created":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T21:35:39Z","timestamp":1619904939000},"page":"4822","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The Kynurenic Acid Analog SZR72 Enhances Neuronal Activity after Asphyxia but Is Not Neuroprotective in a Translational Model of Neonatal Hypoxic Ischemic Encephalopathy"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7474-7148","authenticated-orcid":false,"given":"Vikt\u00f3ria","family":"Kov\u00e1cs","sequence":"first","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, University of Szeged, 6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3448-3835","authenticated-orcid":false,"given":"G\u00e1bor","family":"Remzs\u0151","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, University of Szeged, 6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0973-2473","authenticated-orcid":false,"given":"T\u00edmea","family":"K\u00f6rm\u00f6czi","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Analysis, Interdisciplinary Excellence Center, University of Szeged, 6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9076-2177","authenticated-orcid":false,"given":"R\u00f3bert","family":"Berkecz","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Analysis, Interdisciplinary Excellence Center, University of Szeged, 6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9ria","family":"T\u00f3th-Sz\u0171ki","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, University of Szeged, 6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"P\u00e9nzes","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, University of Szeged, 6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e1szl\u00f3","family":"V\u00e9csei","sequence":"additional","affiliation":[{"name":"Department of Neurology, Interdisciplinary Excellence Center, University of Szeged, 6720 Szeged, Hungary"},{"name":"MTA-SZTE Neuroscience Research Group, Hungarian Academy of Sciences, University of Szeged, 6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5581-2167","authenticated-orcid":false,"given":"Ferenc","family":"Domoki","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, University of Szeged, 6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2431-8-17","article-title":"The TOBY study. Whole body hypothermia for the treatment of perinatal asphyxial encephalopathy: A randomised controlled trial","volume":"8","author":"Azzopardi","year":"2008","journal-title":"BMC Pediatr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.earlhumdev.2010.05.010","article-title":"Epidemiology of neonatal encephalopathy and hypoxic-ischaemic encephalopathy","volume":"86","author":"Kurinczuk","year":"2010","journal-title":"Early Hum. Dev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/pr.2013.206","article-title":"Intrapartum-related neonatal encephalopathy incidence and impairment at regional and global levels for 2010 with trends from 1990","volume":"74","author":"Lee","year":"2013","journal-title":"Pediatr. Res."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Jacobs, S.E., Berg, M., Hunt, R., Tarnow-Mordi, W.O., Inder, T.E., and Davis, P.G. (2013). Cooling for newborns with hypoxic ischaemic encephalopathy. Cochrane Database Syst. Rev., CD003311.","DOI":"10.1002\/14651858.CD003311.pub3"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"5945","DOI":"10.2174\/0929867325666180313113411","article-title":"Ischemic Stroke and Kynurenines: Medicinal Chemistry Aspects","volume":"25","author":"Hertelendy","year":"2018","journal-title":"Curr. Med. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"778","DOI":"10.3389\/fneur.2019.00778","article-title":"Systematic review on the involvement of the kynurenine pathway in stroke: Pre-clinical and Clinical Evidence","volume":"10","author":"Colpo","year":"2019","journal-title":"Front. Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/0304-3940(88)90813-0","article-title":"The excitatory amino acid antagonist kynurenic acid administered after hypoxic-ischemia in neonatal rats offers neuroprotection","volume":"90","author":"Lehmann","year":"1988","journal-title":"Neurosci. Lett."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1038\/jcbfm.1992.57","article-title":"Neuroprotective effects of L-kynurenine on hypoxia-ischemia and NMDA lesions in neonatal rats","volume":"12","author":"Nozaki","year":"1992","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.brainres.2005.11.033","article-title":"Kynurenic acid attenuates NMDA-induced pial arteriolar dilation in newborn pigs","volume":"1069","author":"Bari","year":"2006","journal-title":"Brain Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.brainresrev.2007.05.011","article-title":"Mechanisms involved in the cerebrovascular dilator effects of N-methyl-d-aspartate in cerebral cortex","volume":"56","author":"Busija","year":"2007","journal-title":"Brain Res. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4828","DOI":"10.2174\/092986709789909602","article-title":"Syntheses, Transformations and Pharmaceutical Applications of Kynurenic Acid Derivatives","volume":"16","author":"Fulop","year":"2009","journal-title":"Curr. Med. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/j.neures.2008.04.009","article-title":"The kynurenate analog SZR-72 prevents the nitroglycerol-induced increase of c-fos immunoreactivity in the rat caudal trigeminal nucleus: Comparative studies of the effects of SZR-72 and kynurenic acid","volume":"61","author":"Mihaly","year":"2008","journal-title":"Neurosci. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/s10194-016-0654-5","article-title":"KYNA analogue SZR72 modifies CFA-induced dural inflammation- regarding expression of pERK1\/2 and IL-1\u03b2 in the rat trigeminal ganglion","volume":"17","author":"Warfvinge","year":"2016","journal-title":"J. Headache Pain"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.ejphar.2011.05.069","article-title":"Neuroprotection with a new kynurenic acid analog in the four-vessel occlusion model of ischemia","volume":"667","author":"Fuzik","year":"2011","journal-title":"Eur. J. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"997","DOI":"10.2527\/jas1974.385997x","article-title":"The Fetal and Neonatal Pig in Biomedical Research","volume":"38","author":"Book","year":"1974","journal-title":"Am. J. Anim. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2092","DOI":"10.1177\/0271678X18797328","article-title":"Perinatal hypoxic-ischemic brain injury in large animal models: Relevance to human neonatal encephalopathy","volume":"38","author":"Koehler","year":"2018","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/0378-3782(79)90022-7","article-title":"Comparative aspects of the brain growth spurt","volume":"311","author":"Dobbing","year":"1979","journal-title":"Early Hum. Dev."},{"key":"ref_18","first-page":"141","article-title":"The relationship of arterial blood pH and pCO2 to the viability of the newborn piglet","volume":"35","author":"Randall","year":"1971","journal-title":"Can. J. Comp. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1002\/ana.23647","article-title":"Neonatal encephalopathy: An inadequate term for hypoxic-ischemic encephalopathy","volume":"72","author":"Volpe","year":"2012","journal-title":"Ann. Neurol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1006\/nbdi.2000.0282","article-title":"Neuronal Death in Newborn Striatum after Hypoxia-Ischemia Is Necrosis and Evolves with Oxidative Stress","volume":"7","author":"Martin","year":"2000","journal-title":"Neurobiol. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e2919","DOI":"10.1038\/cddis.2017.318","article-title":"Impaired autophagosome clearance contributes to neuronal death in a piglet model of neonatal hypoxic-ischemic encephalopathy","volume":"8","author":"Cui","year":"2017","journal-title":"Cell Death Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1002\/ana.10402","article-title":"Head cooling with mild systemic hypothermia in anesthetized piglets is neuroprotective","volume":"53","author":"Tooley","year":"2003","journal-title":"Ann. Neurol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1203\/01.PDR.0000072783.22373.FF","article-title":"Hypothermia for 24 hours after asphyxic cardiac arrest in piglets provides striatal neuroprotection that is sustained 10 days after rewarming","volume":"54","author":"Agnew","year":"2003","journal-title":"Pediatr. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"F541","DOI":"10.1136\/archdischild-2014-306284","article-title":"New horizons for newborn brain protection: Enhancing endogenous neuroprotection","volume":"100","author":"Hassell","year":"2015","journal-title":"Arch. Dis. Child. Fetal Neonatal Ed."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1203\/00006450-199412000-00003","article-title":"Delayed (\u201cSecondary\u201d) Cerebral Energy Failure after Acute Hypoxia-Ischemia in the Newborn Piglet: Continuous 48-Hour Studies by Phosphorus Magnetic Resonance Spectroscopy","volume":"36","author":"Lorek","year":"1994","journal-title":"Pediatr. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.brainres.2007.03.083","article-title":"\u201cTherapeutic time window\u201d duration decreases with increasing severity of cerebral hypoxia-ischaemia under normothermia and delayed hypothermia in newborn piglets","volume":"1154","author":"Iwata","year":"2007","journal-title":"Brain Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/0006-8993(82)91048-4","article-title":"An iontophoretic investigation of the actions of convulsant kynurenines and their interaction with the endogenous excitant quinolinic acid","volume":"247","author":"Perkins","year":"1982","journal-title":"Brain Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1111\/j.1471-4159.1989.tb01881.x","article-title":"A Glycine Site Associated with N-Methyl-d-Aspartic Acid Receptors: Characterization and Identification of a New Class of Antagonists","volume":"52","author":"Kessler","year":"1989","journal-title":"J. Neurochem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1113\/jphysiol.1990.sp018288","article-title":"Competitive Antagonists and Partial Agonists At the Glycin Modulatory Site of the Mouse N-methyl-D-aspartate Receptor","volume":"430","author":"Henderson","year":"1990","journal-title":"J. Physiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"7463","DOI":"10.1523\/JNEUROSCI.21-19-07463.2001","article-title":"The Brain Metabolite Kynurenic Acid Inhibits 7 Nicotinic Receptor Activity and Increases Non- 7 Nicotinic Receptor Expression: Physiopathological Implications","volume":"21","author":"Hilmas","year":"2001","journal-title":"J. Neurosci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1111\/jnc.14907","article-title":"Does kynurenic acid act on nicotinic receptors? An assessment of the evidence","volume":"152","author":"Stone","year":"2020","journal-title":"J. Neurochem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1212\/WNL.39.5.713","article-title":"Posthypoxic treatment with MK-801 reduces hypoxic-ischemic damage in the neonatal rat","volume":"39","author":"Hattori","year":"1989","journal-title":"Neurology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.nbd.2011.04.018","article-title":"Neuroprotective effect of acid-sensing ion channel inhibitor psalmotoxin-1 after hypoxia-ischemia in newborn piglet striatum","volume":"43","author":"Yang","year":"2011","journal-title":"Neurobiol. Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1159\/000243878","article-title":"Role of Excitatory Amino Acid Antagonists in the Management of Birth Asphyxia","volume":"62","author":"Levene","year":"1992","journal-title":"Biol. Neonate"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/0304-3940(86)90648-8","article-title":"Inhibition of excitatory neurotransmission with kynurenate reduces brain edema in neonatal anoxia","volume":"71","author":"Simon","year":"1986","journal-title":"Neurosci. Lett."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1016\/j.ntt.2011.07.002","article-title":"On the antioxidant properties of kynurenic acid: Free radical scavenging activity and inhibition of oxidative stress","volume":"33","author":"Maldonado","year":"2011","journal-title":"Neurotoxicol. Teratol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1007\/s00210-011-0605-2","article-title":"Different inhibitory effects of kynurenic acid and a novel kynurenic acid analogue on tumour necrosis factor-\u03b1 (TNF-\u03b1) production by mononuclear cells, HMGB1 production by monocytes and HNP1-3 secretion by neutrophils","volume":"383","author":"Tiszlavicz","year":"2011","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2007","DOI":"10.1111\/j.1471-4159.1991.tb03460.x","article-title":"Blood\u2013Brain Barrier Transport of Kynurenines: Implications for Brain Synthesis and Metabolism","volume":"56","author":"Fukui","year":"1991","journal-title":"J. Neurochem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1002\/(SICI)1097-4547(19990115)55:2<158::AID-JNR3>3.0.CO;2-1","article-title":"Rat model of perinatal hypoxic-ischemic brain damage","volume":"55","author":"Vannucci","year":"1999","journal-title":"J. Neurosci. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.nbd.2008.05.020","article-title":"HIF-1\u03b1 inhibition ameliorates neonatal brain injury in a rat pup hypoxic\u2013ischemic model","volume":"31","author":"Chen","year":"2008","journal-title":"Neurobiol. Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e13467","DOI":"10.1111\/apha.13467","article-title":"Endogenous brain-sparing responses in brain pH and P O2 in a rodent model of birth asphyxia","volume":"229","author":"Pospelov","year":"2020","journal-title":"Acta Physiol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Remzso, G., N\u00e9meth, J., Varga, V., Kov\u00e1cs, V., T\u00f3thSzuki, V., Kaila, K., Voipio, J., and Domoki, F. (2020). Brain interstitial pH changes in the subacute phase of hypoxic-ischemic encephalopathy in newborn pigs. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0240643"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.neuroscience.2013.04.063","article-title":"Post-ischemic treatment with L-kynurenine sulfate exacerbates neuronal damage after transient middle cerebral artery occlusion","volume":"247","author":"Knapp","year":"2013","journal-title":"Neuroscience"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1177\/0333102416678000","article-title":"Effects of kynurenic acid analogue 1 (KYNA-A1) in nitroglycerin-induced hyperalgesia: Targets and anti-migraine mechanisms","volume":"37","author":"Greco","year":"2017","journal-title":"Cephalalgia"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s10194-017-0746-x","article-title":"Topical dura mater application of CFA induces enhanced expression of c-fos and glutamate in rat trigeminal nucleus caudalis: Attenuated by KYNA derivate (SZR72)","volume":"18","author":"Warfvinge","year":"2017","journal-title":"J. Headache Pain"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1007\/s00702-010-0573-6","article-title":"Neuroprotective effects of a novel kynurenic acid analogue in a transgenic mouse model of Huntington\u2019s disease","volume":"118","author":"Nyiri","year":"2011","journal-title":"J. Neural. Transm."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/s00702-011-0692-8","article-title":"Behavioural studies with a newly developed neuroprotective KYNA-amide","volume":"119","author":"Varga","year":"2012","journal-title":"J. Neural. Transm."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.neulet.2013.08.028","article-title":"Paradox effects of kynurenines on LTP induction in the Wistar rat. An in vivo study","volume":"553","author":"Demeter","year":"2013","journal-title":"Neurosci. Lett."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.neulet.2006.03.051","article-title":"Kynurenic acid has a dual action on AMPA receptor responses","volume":"402","author":"Prescott","year":"2006","journal-title":"Neurosci. Lett."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1007\/s00702-008-0052-5","article-title":"The Janus-face kynurenic acid","volume":"115","author":"Robotka","year":"2008","journal-title":"J. Neural. Transm."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1016\/j.pharep.2015.04.015","article-title":"Effect of a kynurenic acid analog on home-cage activity and body temperature in rats","volume":"67","author":"Kassai","year":"2015","journal-title":"Pharmacol. Rep."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Moln\u00e1r, K., L\u0151rinczi, B., Fazakas, C., Szatm\u00e1ri, I., F\u00fcl\u00f6p, F., Kmetyk\u00f3, N., Berkecz, R., Ilisz, I., Krizbai, I.A., and Wilhelm, I. (2021). Szr-104, a novel kynurenic acid analogue with high permeability through the blood\u2013brain barrier. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13010061"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"27","DOI":"10.4103\/0976-0105.177703","article-title":"A simple practice guide for dose conversion between animals and human","volume":"7","author":"Nair","year":"2016","journal-title":"J. Basic Clin. Pharm."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"431","DOI":"10.3389\/fphar.2017.00431","article-title":"Postnatal maturation of the glomerular filtration rate in conventional growing piglets as potential juvenile animal model for preclinical pharmaceutical research","volume":"8","author":"Gasthuys","year":"2017","journal-title":"Front. Pharmacol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1097\/WNP.0b013e31823e96d7","article-title":"The American Clinical Neurophysiology Society\u2019s Guideline on Continuous Electroencephalography Monitoring in Neonates","volume":"28","author":"Shellhaas","year":"2011","journal-title":"J. Clin. Neurophysiol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"American Clinical Neurophysiology Society (2006). Guideline 9B: Guidelines on Visual Evoked Potentials. Am. J. Electroneurodiagn. Technol., 46, 254\u2013274.","DOI":"10.1080\/1086508X.2006.11079585"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Kov\u00e1cs, V., Remzs\u0151, G., T\u00f3th-Sz\u0171ki, V., Varga, V., N\u00e9meth, J., and Domoki, F. (2020). Inhaled H2 or CO2 do not augment the neuroprotective effect of therapeutic hypothermia in a severe neonatal hypoxic-ischemic encephalopathy piglet model. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21186801"},{"key":"ref_58","unstructured":"(2016). Nicolet EEG, Natus Medical Inc."},{"key":"ref_59","first-page":"677","article-title":"Molecular hydrogen affords neuroprotection in a translational piglet model of hypoxic-ischemic encephalopathy","volume":"67","author":"Nemeth","year":"2016","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1097\/WNP.0b013e3182872b24","article-title":"American clinical neurophysiology society standardized EEG terminology and categorization for the description of continuous eeg monitoring in neonates: Report of the american clinical neurophysiology society critical care monitoring committee","volume":"30","author":"Tsuchida","year":"2013","journal-title":"J. Clin. Neurophysiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.jneumeth.2003.10.009","article-title":"EEGLAB: An open source toolbox for analysis of single-trial EEG dynamics including independent component analysis","volume":"134","author":"Delorme","year":"2004","journal-title":"J. Neurosci. Methods"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"18900","DOI":"10.1038\/s41598-019-55468-1","article-title":"NMDA attenuates the neurovascular response to hypercapnia in the neonatal cerebral cortex","volume":"9","author":"Varga","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_63","unstructured":"(2019). LabSolution, LC\/GC 5.97 SP1, Shimadzu."},{"key":"ref_64","unstructured":"(2018). Xcalibur 4.2.28.14, ThermoFisher Scientific."},{"key":"ref_65","unstructured":"Rasband, W. (2020). (Fiji is just) ImageJ 2.1.0\/1.53c, National Institutes of Health."},{"key":"ref_66","unstructured":"(2012). SigmaPlot v12.0, Systat Software."},{"key":"ref_67","unstructured":"(2018). MATLAB R2018b, Mathworks Inc."},{"key":"ref_68","unstructured":"(2020). SPSS 22.0, IBM Corp."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/9\/4822\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:56:35Z","timestamp":1760162195000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/9\/4822"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,1]]},"references-count":68,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["ijms22094822"],"URL":"https:\/\/doi.org\/10.3390\/ijms22094822","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,1]]}}}